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载有地西泮或二甲噻嗪的黏土纳米管通过鼻腔给药在小鼠体内穿透大脑。

Clay Nanotubes Loaded with Diazepam or Xylazine Permeate the Brain through Intranasal Administration in Mice.

机构信息

Center for Biomedical Engineering and Rehabilitation Sciences, Louisiana Tech University, Rustom, LA 71270, USA.

Institute for Micromanufacturing, Louisiana Tech University, Rustom, LA 71270, USA.

出版信息

Int J Mol Sci. 2023 Jun 2;24(11):9648. doi: 10.3390/ijms24119648.


DOI:10.3390/ijms24119648
PMID:37298599
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10253593/
Abstract

The blood-brain barrier (BBB) is an obstacle to the permeation of most therapeutic drugs into the brain, limiting treatments for neurological disorders. Drugs loaded within nanocarriers that pass through the BBB can overcome this limitation. Halloysite consists of naturally occurring biocompatible clay nanotubes of 50 nm diameter and 15 nm lumen, allowing the loading and sustained release of loaded drugs. These have demonstrated the ability to transport loaded molecules into cells and organs. We propose to use halloysite nanotubes as a "nano-torpedo" for drug delivery through the BBB due to their needle-like shape. To determine if they can cross the BBB using a non-invasive, clinically translatable route of administration, we loaded halloysite with either diazepam or xylazine and delivered these intranasally to mice daily over six days. The sedative effects of these drugs were observed in vestibulomotor tests conducted at two, five, and seven days after the initial administration. Behavioral tests were conducted 3.5 h after administration to show that the effects were from halloysite/delivered drugs and not from the drug alone. As expected, the treated mice performed more poorly than the sham, drug alone, and halloysite-vehicle-treated mice. These results confirm that halloysite permeates the BBB to deliver drugs when administered intranasally.

摘要

血脑屏障(BBB)是大多数治疗药物渗透到大脑的障碍,限制了对神经疾病的治疗。装载在能够穿透 BBB 的纳米载体中的药物可以克服这一限制。埃洛石由直径为 50nm 且内腔为 15nm 的天然存在的生物相容性粘土纳米管组成,允许装载药物并持续释放。这些已经证明了将装载分子输送到细胞和器官的能力。由于埃洛石纳米管的针状形状,我们提议将其用作穿透 BBB 的“纳米鱼雷”进行药物递送。为了确定它们是否可以通过非侵入性、可临床转化的给药途径穿过 BBB,我们将地西泮或唑拉西泮装载到埃洛石中,并在六天内每天通过鼻内途径将这些药物递送给小鼠。在初次给药后两天、五天和七天进行前庭运动测试,观察到这些药物的镇静作用。给药后 3.5 小时进行行为测试,以表明这些作用来自埃洛石/递送的药物,而不是来自药物本身。正如预期的那样,与假手术、单独用药和埃洛石载体处理的小鼠相比,接受治疗的小鼠表现更差。这些结果证实,埃洛石经鼻内给药时可以穿透 BBB 来递送药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/7676836539de/ijms-24-09648-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/57609022b7f3/ijms-24-09648-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/d42dc16ea297/ijms-24-09648-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/46647882df42/ijms-24-09648-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/b3aab99b6637/ijms-24-09648-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/69fc2247a4c8/ijms-24-09648-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/a7cb447add9c/ijms-24-09648-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/47890e212eed/ijms-24-09648-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/c07744f069b2/ijms-24-09648-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/eb7e6fd8d4e5/ijms-24-09648-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/7676836539de/ijms-24-09648-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/57609022b7f3/ijms-24-09648-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/d42dc16ea297/ijms-24-09648-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/46647882df42/ijms-24-09648-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/b3aab99b6637/ijms-24-09648-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/69fc2247a4c8/ijms-24-09648-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/a7cb447add9c/ijms-24-09648-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/47890e212eed/ijms-24-09648-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/c07744f069b2/ijms-24-09648-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/eb7e6fd8d4e5/ijms-24-09648-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf25/10253593/7676836539de/ijms-24-09648-g009.jpg

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[4]
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本文引用的文献

[1]
Antimicrobial Nanomaterials Based on Halloysite Clay Mineral: Research Advances and Outlook.

Antibiotics (Basel). 2022-12-6

[2]
Nanomaterials: A Review about Halloysite Nanotubes, Properties, and Application in the Biological Field.

Int J Mol Sci. 2022-9-29

[3]
Evaluation of Recent Intranasal Drug Delivery Systems to the Central Nervous System.

Pharmaceutics. 2022-3-12

[4]
Diazepam causes sedative rather than anxiolytic effects in C57BL/6J mice.

Sci Rep. 2021-4-29

[5]
The Application of Nanotechnology for the Diagnosis and Treatment of Brain Diseases and Disorders.

Front Bioeng Biotechnol. 2021-3-2

[6]
Recent advances in the design of inorganic and nano-clay particles for the treatment of brain disorders.

J Mater Chem B. 2021-3-28

[7]
Evaluation of toxicity of halloysite nanotubes and multi-walled carbon nanotubes to endothelial cells and blood vessels .

Nanotoxicology. 2020-6-23

[8]
Tagged Halloysite Nanotubes as a Carrier for Intercellular Delivery in Brain Microvascular Endothelium.

Front Bioeng Biotechnol. 2020-5-14

[9]
Longitudinal optical imaging technique to visualize progressive axonal damage after brain injury in mice reveals responses to different minocycline treatments.

Sci Rep. 2020-5-8

[10]
Biomedical potential of clay nanotube formulations and their toxicity assessment.

Expert Opin Drug Deliv. 2019-9-12

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